title: The cytokine-driven regulation of secretoglobins in normal human upper airway and their expression, particularly that of uteroglobin-related protein 1, in chronic rhinosinusitis.
abstract: BACKGROUND
  The involvement of secretoglobins (SCGBs) other than SCGB1A1 (Clara cell 10-kDa protein, CC10) in human airway diseases remains unexplored. Among those SCGBs, SCGB3A2 (uteroglobin-related protein 1, UGRP1) is particularly interesting, given its structure and function similarities with SCGB1A1 (CC10). The aim of this study was to investigate the expression regulation of SCGBs other than SCGB1A1 (CC10) in human upper airway, and their potential involvement, particularly that of SCGB3A2 (UGRP1), in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP).
  
  
  METHODS
  Eight SCGB family members including SCGB3A2 (UGRP1), SCGB1C1 (ligand binding protein RYD5), SCGB1D1 (lipophilin A), SCGB1D2 (lipophilin B), SCGB1D4 (interferon-γ inducible SCGB), SCGB2A1 (mammaglobin 2), SCGB2A2 (mammaglobin 1), and SCGB3A1 (uteroglobin-related protein 2) were studied. The regulation of SCGBs mRNA expression in normal nasal mucosa by proinflammatory, Th1, and Th2 cytokines was studied through nasal explant culture. SCGBs mRNA expression levels in CRSsNP and CRSwNP patients and controls were compared. The mRNA levels were detected by means of quantitative reverse transcriptase-polymerase chain reaction. The protein expression of SCGB3A2 (UGRP1) was analyzed using immunohistochemistry.
  
  
  RESULTS
  The expression of SCGBs except SCGB1D2 (lipophilin B) could be found in upper airway and be differentially regulated by different cytokines. SCGB3A2 (UGRP1) mRNA expression was induced by Th1 cytokine, but suppressed by proinflammatory and Th2 cytokines. SCGBs mRNA expression was altered in CRS; particularly, SCGB3A2 (UGRP1) protein and mRNA expression was markedly decreased in both CRSsNP and CRSwNP and its protein levels inversely correlated with the number of total infiltrating cells, preoperative sinonasal CT scores, and postoperative endoscopy and symptom scores.
  
  
  CONCLUSIONS
  SCGBs except SCGB1D2 (lipophilin B) are expressed in human upper airway and their expression can be differentially regulated by inflammatory cytokines. SCGBs mRNA expression is altered in CRS. Reduced production of UGRP1, which is likely due, at least in part, to a local cytokine environment, may contribute to the hyper-inflammation in CRS and correlates with response to surgery.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Lu
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Long
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: You
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Cui
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000328:Adult; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009298:Nasal Polyps / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012220:Rhinitis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D060765:Secretoglobins; D012852:Sinusitis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D046509:Tissue Culture Techniques; D014598:Uteroglobin / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; C449940:SCGB3A2 protein, human; D060765:Secretoglobins; D014598:Uteroglobin